ABSTRACT

Glucagon-Like Peptide-1 (GLP-1) is an important peptide hormone secreted by L-cells in the gastrointestinal tract in response to nutrients. It is produced by the differential cleavage of the proglucagon peptide. GLP-1 elicits a wide variety of physiological responses in many tissues that contribute to metabolic homeostasis. For these reasons, therapies designed to either increase endogenous GLP-1 levels or introduce exogenous peptide mimetics are now widely used in the management of diabetes. In addition to GLP-1 production from L-cells, recent reports suggest that pancreatic islet alpha cells may also synthesize and secrete GLP-1. Intra-islet GLP-1 may therefore play an unappreciated role in islet health and glucose regulation, suggesting a potential functional paracrine role for islet-derived GLP-1. In this review, we assess the current literature from an islet-centric point-of-view to better understand the production, degradation, and actions of GLP-1 within the endocrine pancreas in rodents and humans. The relevance of intra-islet GLP-1 in human physiology is discussed regarding the potential role of intra-islet GLP-1 in islet health and dysfunction.

摘要

Glucagon-Like Peptide-1 (GLP-1) 是一种重要的肽激素，由胃肠道中的 L 细胞响应营养物质而分泌。它是由胰高血糖素原肽的差异切割产生的。GLP-1 在许多有助于代谢稳态的组织中引发多种生理反应。由于这些原因，旨在提高内源性 GLP-1 水平或引入外源性肽模拟物的疗法现在被广泛用于糖尿病的管理。除了从 L 细胞产生 GLP-1 外，最近的报告表明胰岛 α 细胞也可能合成和分泌 GLP-1。因此，胰岛内 GLP-1 可能在胰岛健康和葡萄糖调节中发挥不被重视的作用，这表明胰岛衍生的 GLP-1 具有潜在的功能性旁分泌作用。在本次审查中，我们从以胰岛为中心的角度评估当前文献，以更好地了解 GLP-1 在啮齿动物和人类内分泌胰腺中的产生、降解和作用。关于胰岛内 GLP-1 在胰岛健康和功能障碍中的潜在作用，讨论了胰岛内 GLP-1 在人体生理学中的相关性。